Sickle cell disease (SCD) is a major health problem, affecting approximately 1 in 600 African Americans. Although newborn screening and improvements in care have resulted in more favorable long-term prognosis, most people with this disease still encounter frequent unpredictable episodes of pain over their life span. The aim of this project is to evaluate perceptual and cognitive aspects of the SCD pain experience by capitalizing on recent advances in knowledge of both typical and altered pain processing. The approach is holistic in that multiple processes, ranging from sensory to cognitive, will be examined. The episodic nature of SCD pain will enable reversible and irreversible components of altered processing to be distinguished. Four pain processes will be studied: (1) temporal summation, a gradual increase in the intensity of pain from a continuing stimulus; (2) intensity discrimination, the clinically valuable ability to detect changes in the level of pain; (3) diffuse noxious inhibitory controls (DNIC), a process in which one pain is reduced in the presence of another, generally more intense, pain; and (4) hypervigilance, a perceptual tendency to attend excessively to, and perceptually amplify, pain and other unpleasant sensations. Taken together, experiments on these processes will begin to give a vertically-integrated picture of SCD pain processing. Pain processing will be assessed in 40 individuals with SCD, and 40 pain-free controls. Experimental pain will be produced with pressure applied to a finger-a safe, effective method used in our prior SCD research. The robustness of each process in SCD patients will be assessed (a) relative to controls, and (b) during different clinical pain states. Auditory stimuli, and social/behavioral psychometric instruments, will be used in other aspects of the study. Partially-reversible alterations of pain processing (increased temporal summation and hypervigilance; decreased pain discrimination and DNIC) are expected to be found in SCD, based on a two-stage model of SCD pain episodes that is proposed here. The long-term goals of this project are: (1) to obtain experimental evidence that will contribute to a holistic understanding of pain processing in SCD; (2) to develop and validate novel biobehavioral approaches that will permit quantitative assessment of perceptual and cognitive factors in pain processing; and (3) to provide a scientific basis for behavioral and cognitive interventions that will contribute to the alleviation of SCD pain. The intense and unpredictable pain caused by sickle cell disease is a major public health problem. This research will increase understanding of biological and psychological processes that affect the severity of this pain, laying a foundation for new behavioral and cognitive strategies to alleviate it. [unreadable] [unreadable] [unreadable]